G-protein biased signaling agonists of Dopamine D3 receptor promote distinct activation patterns of ERK1/2.
Biased signaling
Dopamine D3 receptors
Dual phosphorylation
ERK1,2
G-protein signaling
Mono phosphorylation
Pramipexole
Protein Kinase C
SK609
β-arrestin 2
Journal
Pharmacological research
ISSN: 1096-1186
Titre abrégé: Pharmacol Res
Pays: Netherlands
ID NLM: 8907422
Informations de publication
Date de publication:
05 2022
05 2022
Historique:
received:
15
02
2022
revised:
31
03
2022
accepted:
10
04
2022
pubmed:
17
4
2022
medline:
25
5
2022
entrez:
16
4
2022
Statut:
ppublish
Résumé
Dopamine D3 receptors (D3R) have a causal role in neurological and psychiatric disorders. We have developed a novel class of G-protein biased (GPB) signaling D3R agonists with minimal β-arrestin2 (βarr2) recruitment and demonstrated efficacy in rodent model of Parkinson's disease. This contrasts with unbiased (UB) D3R agonists like Pramipexole which recruit both β-arrestin and G-proteins for signaling. In this study, we investigated the effects of GPB and UB agonists on D3R mediated activation of mono and dual phosphorylation of ERK1/2. We used the neuronal-like SH-SY5Y cells stably expressing D3R and βarr2 knockdown (βarr2KD) to delineate the roles of G
Identifiants
pubmed: 35429668
pii: S1043-6618(22)00168-2
doi: 10.1016/j.phrs.2022.106223
pii:
doi:
Substances chimiques
Dopamine Agonists
0
Receptors, Dopamine D3
0
beta-Arrestin 2
0
beta-Arrestins
0
GTP-Binding Proteins
EC 3.6.1.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
106223Subventions
Organisme : NINDS NIH HHS
ID : R44 NS117201
Pays : United States
Informations de copyright
Copyright © 2022 Elsevier Ltd. All rights reserved.